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Abstract

Monitoring the onset of erythema following external beam radiation therapy has the potential to offer a means of managing skin toxicities via biological targeted agents – prior to full progression. However, current skin toxicity scoring systems are subjective and provide at best a qualitative evaluation. Here, we investigate the potential of diffuse optical spectroscopy (DOS) to provide quantitative metrics for scoring skin toxicity. A DOS fiberoptic reflectance probe was used to collect white light spectra at two probing depths using two short fixed source-collector pairs with optical probing depths sensitive to the skin surface. The acquired spectra were fit to a diffusion theory model of light transport in tissue to extract optical biomarkers (hemoglobin concentration, oxygen saturation, scattering power and slope) from superficial skin layers of nude mice, which were subjected to erythema inducing doses of ionizing radiation. A statistically significant increase in oxygenated hemoglobin (p < 0.0016) was found in the skin post-irradiation – confirming previous reports. More interesting, we observed for the first time that the spectral scattering parameters, A (p = 0.026) and k (p = 0.011), were an indicator of erythema at day 6 and could potentially serve as an early detection optical biomarker of skin toxicity. Our data suggests that reflectance DOS may be employed to provide quantitative assessment of skin toxicities following curative doses of external beam radiation.

An operational schematic of the fiberoptic probe employed. Broadband light is used to illuminate the tissue (via an optical fiber) and diffuse reflectance spectra are collected at a fixed distance from the source via a collection fiber.

Typical white light reflectance spectra of non-irradiated (top) and irradiated (bottom) mouse skin 6 days post irradiation. Thin blue lines are the measured data while solid green lines are the respective fits. Excellent agreement between measurement and fits were typically observed. Two key differences were seen between the two groups: 1) an overall increase in absolute reflectance and 2) a distinct change in spectral shape between 550 – 600 nm.

Change in the oxygenation fraction for the non-irradiated group (top) and irradiated group (bottom). Individual mouse points are shown along with the average (black bar) and error bars depicting standard deviation. The baseline-normalized mean difference between the two groups (per mouse) is significant for Days 6-12 as shown in Table 2.

Top and bottom left show the relative time-resolved changes in A and k for the control group. Top and bottom right depict the same for the irradiated group. The change in A and k on Day 6 was found to be significant (p < 0.026).